The contribution of major histocompatibility complex contacts to the affinity and kinetics of T cell receptor binding.
Sci Rep
; 6: 35326, 2016 10 13.
Article
em En
| MEDLINE
| ID: mdl-27734930
ABSTRACT
The interaction between the T cell antigen receptor (TCR) and antigenic peptide in complex with major histocompatibility complex (MHC) molecules is a crucial step in T cell activation. The relative contributions of TCRpeptide and TCRMHC contacts to the overall binding energy remain unclear. This has important implications for our understanding of T cell development and function. In this study we used site directed mutagenesis to estimate the contribution of HLA-A2 side-chains to the binding of four TCRs. Our results show that these TCRs have very different energetic 'footprints' on HLA-A2, with no residues contributing to all TCR interactions. The estimated overall contribution of MHC side-chains to the total interaction energy was variable, with lower limits ranging from 11% to 50%. Kinetic analysis suggested a minor and variable contribution of MHC side-chains to the transition state complex, arguing against a two-step mechanism for TCR binding.
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Base de dados:
MEDLINE
Assunto principal:
Receptores de Antígenos de Linfócitos T
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Linfócitos T
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Antígeno HLA-A2
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Complexo Principal de Histocompatibilidade
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article